Summary
Contrast echocardiography with sonicated radiographic contrast agents has been used for the qualitative and quantitative determination of myocardial blood flow. One major problem has been the size of the microbubbles since only bubbles smaller than 8 µm are expected to pass the capillary bed and larger bubbles may obstruct the capillaries and, thus, alter myocardial blood flow. These techniques have been used for several years, but their reliability has not yet been assessed accurately. Five different methods for the production of sonicated radiographic contrast agents (methods 1–3 from the literature, and 4 and 5 from our laboratory; M1–5) were evaluated for their use in quantitative contrast echocardiography. The sonication of non-ionic X-ray contrast media was performed with a standard titanium probe (20 kHz) for methods 1–4, with variation in the sonication time and the number of sonication jets used for each method. In M5, we used bubbles that were produced by the insufflation of oxygen in the X-ray contrast agent; large (>8 µm) bubbles were destroyed by sonication at 380kHz (resonance method). Mean bubble size was determined by computerized videomicroscopy. The effect of bubble size on the backscatter of the ultrasonic signal was calculated for each method. Mean bubble size (±1 SD) ranged between 11.5 ± 4µm and 16.1 ± 14 µm for M1–M5. The best values, i.e., the smallest bubbles, were found with M4 (prepressurized contrast medium). Assuming capillary passage for bubbles smaller than 8 µm, only 14%–48% of the bubbles were smaller than 8 µm (M1–M5). The best results with regard to bubble size (≤8 µm) were observed with M5 (48% ≤8 µm). In regard to the influence of bubble size on the backscatter of the ultrasonic signal, 56%–98.5% of the signal was produced by bubbles larger than 15 µm (M1–5) but the best results were obtained with M4. It is concluded that capillary-passage of sonicated microbubbles (≤8 µm) can be expected in only 14%–48% of the bubbles for the five different sonication techniques. More than 50% of all microbubbles produced by these techniques are larger than the expected 8 µm. These large bubbles are responsible for the backscatter of the ultrasonic signal in the vast majority of cases. Thus, the sonication of radiographic contrast agents appears to be inappropriate for the production of uniformly small microbubbles and, thus, this method is not suitable for quantitative measurements of coronary blood flow.
Similar content being viewed by others
References
Lim Y-J, Nanto S, Masuyama T, Kodama K, Ikeda T, Kitabatake A, Kamada T (1989) Visualization of subendocardial myocardial ischemia with myocardial contrast echocardiography in humans. Circulation 79(2):233–244
Kemper AJ, Force T, Kloner R, Gilfoil M, Perkins L, Hale S, Alker K, Parisi AF (1985) Contrast echocardiographic estimation of regional myocardial blood flow after acute coronary occlusion. Circulation 72(5):1115–1124
Kaul S, Glasheen W, Ruddy TD, Pandian NG, Weyman AE, Okada RD (1987) The importance of defining left ventricular area at risk in vivo during acute myocardial infarction: An experimental evaluation with myocardial contrast two-dimensional echocardiography. Lab Invest 75(6):1249–1260
Keller MW, Feinstein SB, Briller RA, Powsner SM (1986) Automated production and analysis of echo contrast agents. J Ultrasound Med 5:493–498
Zwehl W, Sauer W, Klauss V, Angermann CE, Theisen K (1989) Mikrobläschen in Farb-Doppler-und Kontrast-Echocardiographie. In: Grube E (ed) Problem der Myokard-Kontrastechokardiographie. Thieme Verlag, Stuttgart, pp. 345–354
Feinstein SB (1986) Myocardial perfusion imaging: Contrast echocardiography today and tomorrow. J Am Coll Cardiol 8(1):251–253
Feinstein SB, Lang RM, Dick C, Neumann A, Al-Sadir J, Chua KG, Carroll J, Feldman T, Borow KM (1988) Contrast echocardiography during coronary arteriography in humans: Perfusion and anatomic studies. J Am Coll Cardiol 11(1):59–65
Meerbaum S (1988) Myocardial contrast two-dimensional echocardiography: A complement to coronary angiography. J Am Coll Cardiol 12(4):935–936
Feinstein SB, Shah PM, Bing RJ, Meerbaum S, Corday E, Chang B-L, Santillan G, Fujibayashi Y (1984) Microbubble dynamics visualized in the intact capillary circulation. J Am Coll Cardiol 4(3):595–600
Keller MW, Glasheen W, Smucker ML, Burwell LR, Watson DD, Kaul S (1988) Myocardial contrast echocardiography in humans. II. Assessment of coronary blood flow reserve. J Am Coll Cardiol 12(4):925–934
Kaul S (1992) Clinical applications of myocardial contrast echocardiography. Am J Cardiol 69:46H–55H
Mudra H, Klauss V, Metz J, Meissner O, Zwehl W, Theisen K (1992) Myocardiale Kontrastechokardiographie zur Verlaufskontrolle nach perkutaner transluminaler Koronarangioplastie. Dtsch Med Wschr 117(36):1343–1349
Rovai D, Ghelardini G, Lombardi M, Trivella MG, Nevola E, Taddei L, Michelassi C, Distante A, DeMaria AN, L'Abbate A (1992) Myocardial washout of sonicated iopamidol reflects coronary blood flow in the absence of autoregulation. J Am Coll Cardiol 20(6):1417–1424
Klauss V, Meissner O, Metz J, Theisen K, Mudra H (1993) Kontrastechokardiographie zur Beurteilung der myokardialen Flussreserve. Z Kardiol 82:799–806
Kaul S, Jayaweera AR, Glasheen WP, Villanueva FS, Gutgesell HP, Spotnitz WD (1992) Myocardial contrast echocardiography and the transmural distribution of flow: A critical appraisal during myocardial ischemia not associated with infarction. J Am Coll Cardiol 20(4):1005–1016
Cheirif J, Zoghbi WA, Raizner AE, Minor ST, Winters WL, Klein MS, De Bauche TL, Lewis JM, Roberts R, Quinones MA (1988) Assessment of myocardial perfusion in humans by contrast echocardiography; I. Evaluation of regional coronary reserve by peak contrast intensity. J Am Coll Cardiol 11(4):735–743
Shapiro JR, Reisner SA, Amico AF, Kelly PF, Meltzer RS (1990) Reproducibility of quantitative myocardial contrast echocardiography. J Am Coll Cardiol 15(3):602–609
Klauss V, Mudra H, Meissner O, Metz J, Theisen K (1992) Myocardiale Kontrastechokardiographie: Reproduzierbarkeit von videodensitometrischen Washout-Variablen. Z Kardiol 81:29 (abstr.)
Lang RM, Feinstein SB, Feldman T, Neumann A, Chua KG, Borow KM (1986) Contrast echocardiography for evaluation of myocardial perfusion: Effects of coronary angioplasty. J Am Coll Cardiol 8(1):232–235
Ten Cate FJ, Cornel JH, Serruys PW, Vletter WB, Roelandt J, Mittertreiner WH (1987) Quantitative assessment of myocardial blood flow by contrast twodimensional echocardiography: Initial clinical observations. Am J Physiol Imag (2):56–60
Zwehl W (1990) Kontrast-Echokardiographie zur Bestimmung der Myokardperfusion. Habilitationsschrift, Medizinische Klinik Innenstadt der Ludwig-Maximilians-Universität, München
Lazarov MP, Mayer IV, Mayer St M (1993) Vorrichtung und Verfahren zur Steuerung der Grössenverteilungen von Gas- oder Flüssigkeitsblasen in einem flüssigen Medium. Deutsches Patentamt, DE 4305 660 A1
Apfel RE (1981) Acoustic cavitation prediction. J Acoust Soc Am 69(6):1624–1633
Vandenberg BF, Feinstein S, Kieso RA, Hunt M, Kerber RE (1988) Myocardial risk area and peak gray level measurement by contrast echocardiography: Effect of microbubble size and concentration, injection rate, and coronary vasodilation. Am Heart J 115(4):733–739
Feinstein SB, Ten Cate FJ, Zwehl W, Ong K, Maurer G, Tei C, Shah PM, Meerbaum S, Corday E (1984) Two-dimensional contrast echocardiography; I. In vitro development and quantitative analysis of echo contrast agents. J Am Coll Cardiol 3(1):14–20
Ten Cate FJ, Feinstein S, Zwehl W, Meerbaum S, Fishbein M, Shah PM, Corday E (1984) Two-dimensional contrast echocardiography; II. Transpulmonary studies. J Am Coll Cardiol 3(1):21–27
Shapiro JR, Xie F, Meltzer RS (1988) Myocardial contrast two-dimensional echocardiography: Dosemyocardial effect relations of intracoronary microbubbles. J Am Coll Cardiol 12(3):765–771
Porter TR, D'Sa A, Turner C, Jones LA, Minisi AJ, Mohanty PK, Vetrovec GW, Nixon JV (1993) Myocardial contrast echocardiography for the assessment of coronary blood flow reserve: Validation in humans. J Am Coll Cardiol 21(2):349–355
Rovai D, Lombardi M, Distante A, L'Abbate A (1991) Myocardial perfusion by contrast echocardiography from off-line processing to radio frequency analysis. Circulation 85(Suppl. III.):97–103
Rovai D, Ghelardini G, Trivella MG, Björklund F, Nevola E, Taddei L, Distante A, L'Abbate A (1993) Intracoronary air-filled albumin microspheres for myocardial blood flow measurements. J Am Coll Cardiol 22(7):2014–2021
Cheirif J, Zoghbi WA, Bolli R, O'Neill PG, Hoyt BD, Quinones MA (1989) Assessment of regional myocardial perfusion by contrast echocardiography; II. Detection of changes in transmural and subendocardial perfusion during dipyridamole-induced hyperemia in a model of critical coronary stenosis. J Am Coll Cardiol 14(6):1555–1565
Rovai D, Ghelardini G, Lombardi M, Trivella MG, Nevola E, Federghini EM, Distante A, L'Abbate A (1993) Myocardial washout of sonicated iopamidol does not reflect the transmural distribution of coronary blood flow. Eur Heart J 14(8):1072–1078
Jayaweera AR, Matthew TL, Spotnitz WD, Watson DD, Kaul S (1990) Method for the quantitation of myocardial perfusion during myocardial contrast twodimensional echocardiography. J Am Soc Echocardiogr 3(2):91–97
Keller MW, Segal SS, Kaul S, Duling B (1989) The behavior of sonicated albumin microbubbles within the microcirculation: A basis for their use during myocardial contrast echocardiography. Circ Res 65(2):458–467
Wiencek JG, Feinstein SB, Walker R, Aronson S (1988) Pitfalls in quantitative contrast echocardiography: The steps to quantitation of perfusion. J Am Coll Cardiol 11(1):59–65
Ishimaru A (1978) Wave propagation and scattering in random media. Academic, New York, pp 1–67
Powsner SM, Keller MW, Sanjie J, Feinstein SB (1986) Quantitation of echocontrast effects. Am J Physiol Imag 1:124–128
Alliger H (1980) New methods in ultrasonic processing. Reprinted in Am Laboratory Sept.:1–6
Alliger H (1975) Ultrasonic disruption. Reprinted in Am Laboratory Oct.:1–8
Neppiras EA (1980) Acoustic cavitation. Physics Reports 61(1):159–251
Willard GW (1953) Ultrasonically induced cavitation in water: A step by step process. J Acoust Soc Am 25:669–686
Klein AL, Bailey AS, Moura A, Murray RD, Morehead AJ, Brum J, Pearce G, Stewart WJ, Thomas JD (1993) Reliability of echocardiographic measurements of myocardial perfusion using commercially produced sonicated serum albumin (albunex). J Am Coll Cardiol 22(7):1983–1993
Shapiro JR, Reisner SA, Lichtenberg GS, Meltzer RS (1990) Intravenous contrast echocardiography with use of sonicated albumin in humans: Systolic disappearance of left ventricular contrast after transpulmonary transmission. J Am Coll Cardiol 16(7):1603–1607
Keller MW, Glasheen W, Kaul S (1989) Albunex: A safe and effective commercially produced agent for myocardial contrast echocardiography. J Am Soc Echocardiogr 2(1):458–467
Schneider M, Bussat P, Barrau M-B, Arditi M, Yan F, Hybl E (1992) Polymeric microballoons as ultrasound contrast agents. Invest Radiol 27:134–139
De Jong N, Hoff L, Skotland T, Bom N (1992) Absorption and scatter of encapsulated gas-filled microspheres: Theoretical considerations and some measurements. Ultrasonics 30(2):95–103
Author information
Authors and Affiliations
Additional information
Supported by the Swiss Cardiology Foundation
Rights and permissions
About this article
Cite this article
Mayer, I.V., Lazarov, M.P., Utzinger, U. et al. Sonicated X-ray contrast agents for quantitative myocardial contrast echocardiography — a critical approach. Heart Vessels 10, 96–105 (1995). https://doi.org/10.1007/BF01744500
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01744500